Long term goals & rationale. In mammals, information about the visual world is transmitted from the eye to more than 10 distinct brain nuclei by at least 20 different retinal ganglion cell classes. These diverse classes include brisk small and large receptive field types, directionally and orientationally selective, suppressed-by-contrast and edge detecting cells. Both the underlying retinal circuitry responsible for these ganglion cell response properties, and their function in vision, including specific central projections, remain poorly known. Because the diversity of mammalian retinal ganglion cell classes is best known in rabbit, it is the species of choice for the study of complex receptive field (RF) types in mammals, and their underlying retinal circuitry, structure-function relationships, retinal distribution, neurotransmitters and CNS projections. Differential diagnosis of eye diseases (many of which directly involve retinal ganglion cells and their axons) may depend critically on understanding the "trigger features" particular to each ganglion cell class, the underlying retinal circuitry and neurotransmitters associated with each class, and their central projections. Research design and methods. The proposed study will use both extracellular recording and intracellular recording and staining of ganglion cells and cholinergic (Ach) amacrine cells using the isolated rabbit retina preparation to understand the retinal distribution, neurotransmitters, and physiological mechanisms (particularly cholinergic inputs) underlying the responses of the On-Off and On directionally selective (DS) ganglion cells, and other complex receptive field types in rabbit. Specific aims of this research proposal for complex RF ganglion cells (especially DS types) are to: 1. Determine details of the retinal distribution and coverage (tiling) of complex RF ganglion cell classes, particularly On Off and On DS ganglion cells, by intracellular staining of nearest neighbors. 2. Quantitatively investigate the connectivity between cholinergic amacrine cells and DS ganglion cells by intracellularly staining Ach amacrines on the preferred and null-direction sides of DS ganglion cells. 3. Quantitatively investigate RF properties, particularly motion facilitation and inhibition of DS ganglion cell responses, by pharmacological manipulation of cholinergic and GABAergic inputs. 4. Record intracellularly from DS ganglion cells to determine presynaptic inputs mediating their responses. 5. Determine the central projections of complex RF ganglion cells, esp.DS ganglion cells, by CNS injections of retrograde fluorescent tracers prior to recording and staining in the isolated retina preparation.